Abstract: Provided herein, in some embodiments, are nucleic acid constructs encoding therapeutic proteins of interest comprising one or more alternatively-spliced exons that regulate the expression of therapeutic proteins of interest. Such constructs may in some embodiments be useful for delivery in a recombinant viral vector.

Abstract: Autoregulatory systems that have been implemented to control the expression and activity of Cast 3d, including the activity of Cast 3d in vivo, thereby reducing collateral damage in cells at off-target sites (e.g., non-target messenger RNA transcripts. The autoregulatory system is in the form of a nucleic acid molecule comprising a zinc finger binding site, a promoter, and a nucleotide sequence encoding a Cast 3d fusion protein, and a transcriptional repressor domain, and wherein the Cast 3d fusion protein binds to the zinc finger binding site and represses transcription of the nucleotide sequence encoding the Cast 3d fusion protein.

Abstract: Aspects of the disclosure relate to methods and compositions (e.g., biomarkers) useful for diagnosing pre- symptomatic amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), and for monitoring the progression of ALS/FTD in subjects diagnosed with the disease. Methods of treating neurodegenerative diseases (e.g., ALS/FTD) are also described.

Abstract: Provided herein, in some embodiments, are nucleic acid constructs encoding RNA molecules comprising one or more introns that can be regulated (e.g., autoregulated), and that are useful for delivery in a recombinant viral vector. Aspects of the application provide compositions and methods for delivering regulated (e.g., auto-regulated) gem expression constructs to a subject.

Abstract: Disclosed are methods of treating a disorder or disease associated with myotonic dystrophy. Methods of treating a CNS dysfunction and/or cognitive impairment associated with myotonic dystrophy in a subject comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed. Methods of treating a myotonic dystrophy associated disease or disorder caused by mis-splicing of GABRG2 in a subject comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed. Methods of improving cognitive function or alertness in a subject having myotonic dystrophy comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed.

Abstract: Disclosed herein are compositions and methods for treating diseases characterized by expanded microsatellite repeats by impeding or inhibiting transcription of expanded microsatellite repeats.

Abstract: Disclosed are methods of treating a disorder or disease associated with myotonic dystrophy. Methods of treating a CNS dysfunction and/or cognitive impairment associated with myotonic dystrophy in a subject comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed. Methods of treating a myotonic dystrophy associated disease or disorder caused by mis-splicing of GABRG2 in a subject comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed. Methods of improving cognitive function or alertness in a subject having myotonic dystrophy comprising administering a therapeutically effective amount of a GABAA receptor antagonist or inverse agonist to the subject are disclosed.